20 Dermatology
Hyperhidrosis
Hyperhidrosis is a condition characterised by abnormally increased sweating, in excess of
that required for regulation of body temperature. Hyperhidrosis can either be generalised
or localised to specifc parts of the body, such as hands, feet and axillae. Hyperhidrosis can
be divided into primary or idiopathic, and a secondary type. Te primary type usually starts
during adolescence or even earlier, while secondary hyperhidrosis can start at any point in life.
Te latter form may be due to a disorder of the thyroid or pituitary gland, diabetes mellitus,
tumours, gout, menopause, or certain medications. Tis article highlights the clinical features
and the treatment options for this condition.
Nabil Aly, Consultant Physician, University Hospital Aintree, Liverpool
email nmaly@doctors.org.uk
Hyperhidrosis is sweating in
excess of that required for
normal thermoregulation. It is a
condition that usually begins in
either childhood or adolescence
and can affect any site on the
body. However, the sites most
commonly afected are the palms,
soles, and axillae. Excessive
sweating may be primary
(idiopathic) or secondary to
medication use, certain diseases,
metabolic disorders, or febrile
illnesses. Hyperhidrosis often
causes great emotional distress
and occupational disability
for the patient, regardless of
the form and the extent of the
problem. Hyperhidrosis is
difcult to treat efectively. With
the newer treatment modalities
now available, the patient has
numerous options and is ofered
a better prognosis.
Types
Hyperhidrosis exists in three forms:
emotionally induced hyperhidrosis,
which affects palms, soles, and
GM | Midlife and Beyond | June 2012
axillae; localised hyperhidrosis,
and generalised hyperhidrosis.1,2
Localised hyperhidrosis, unlike
generalised hyperhidrosis,
usually begins in childhood or
adolescence. Localised unilateral
or segmental hyperhidrosis is
rare and of unknown origin.
The condition usually presents
on the forearm or forehead in
otherwise healthy individuals,
without evidence of the typical
triggering factors found in
essential hyperhidrosis. Unilateral
hyperhidrosis with accompanying
contra-lateral anhidrosis is also
rare.3 Palmar hyperhidrosis is a
benign functional disorder that
is a psychological and social
handicap. Harlequin syndrome
is characterised by unilateral
hyperhidrosis and flushing,
predominantly induced by heat
or exercise. 4 The sympathetic
defcits are usually limited to the
face.4 Night sweats among older
people could be related to certain
systemic conditions and clinical
assessment is always required
to rule out the presence of these
causes (Box 1).
Epidemiology
People of all ages can be afected
by hyperhidrosis. Primary
hyperhidrosis affects men
and women equally, and most
commonly occurs among people
aged 25–64 years. Some may
have been affected since early
childhood, and about 30–50%
have another family member
afflicted, implying a genetic
predisposition.5 Localised
hyperhidrosis, unlike generalised
hyperhidrosis, usually begins in
childhood or adolescence. In a
study of 850 patients with palmar,
axillary, or facial hyperhidrosis,
62% of patients reported that
sweating began since before
they could remember; 33%
since puberty; and 5% during
adulthood. 6 In a cross-sectional
primary care study among 795
older patients (older than 64
years), 10% reported being
bothered by night sweats, 9%
by day sweats, and 8% by hot
flushes. 7 All three symptoms
were associated with reduced
quality of life.7
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Dermatology 21
Box 1: Common causes of night sweats among older patients
Te condition
Menopause
Pulmonary tuberculosis (TB)
Diabetes mellitus
Medications*
Lymphoma
Parkinson’s disease
Mental disorder/stress
Clinical features
Women would also experience
hot fushes
Usually associated with fatigue
and anorexia
However, atypical presentation is
not uncommon
Tis type of hyperhidrosis could
be a manifestation of autonomic
dysfunction
Several medications may induce
excessive sweating at night
In general, the drugs listed
below can be associated with
hyperhidrosis
Nights sweats are a symptom of
certain types of Hodgkin’s disease
found in older patients
Te condition can be associated
with localised or generalised
hyperhidrosis
Anxiety and depression may cause
night sweats
* These include: Calcitonin, fentanyl, acyclovir, ceftriaxone, levothyroxine,
levodopa and carbidopa, quetiapine, amlodipine, omeprazole, insulin,
medroxyprogesterone, testosterone, prednisolone and tamoxifen.
Pathophysiology
Te pathophysiology underlying
hyperhidrosis is complex and
not well understood. Tere are
two distinct types of sweating:
thermal sweating, which tends
to occur on the trunk and is
controlled by the hypothalamus
via the thermo-sensitive preoptic
sweat centre, and emotional
sweating, which is predominately
on the palms and soles and
is regulated by the cerebral
cortex. Thermoregulation and
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sweat production are mainly
controlled by the cerebral cortex,
anterior hypothalamus and the
sympathetic nervous system. In
addition, there are three types of
sweat glands: eccrine, apocrine
and apoeccrine. The eccrine
type is the most numerous type,
predominantly occurring on the
soles of the feet, palms, axilla and
face, and this type is innervated by
the sympathetic nervous system,
with acetylcholine as the principle
neurotransmitter. 8 Apocrine
glands are androgen-dependent,
less numerous and are found in
the axilla and genital regions. Te
apoeccrine glands are found only
in the adult axilla. Te eccrine
type is the one mainly involved
in hyperhidrosis. Hyperhidrosis
is usually stimulated by emotion
and stress, so it does not occur
during sleep or sedation. While
normal sweating is controlled
primarily by thermoregulation
and, thus, occurs independently
of level of consciousness. The
primary defect in patients
with hyperhidrosis may be
hypothalamic hypersensitivity
to emotional stimuli from the
cerebral cortex. 8 Generalised
hyperhidrosis may be the
consequence of autonomic
dysregulation, or it may develop
secondary to a metabolic
disorder, febrile illness, or
malignancy. In its localised form,
hyperhidrosis may result from a
disruption followed by abnormal
regeneration of sympathetic
nerves or a localised abnormality
in the number or distribution of
the eccrine glands, or it may be
associated with other (usually
vascular) abnormalities. When
caused by stress, hyperhidrosis
may be generalised or limited to
the palms, soles, and forehead.8
Aetiology
Hyperhidrosis can be idiopathic
or sometimes secondary to other
diseases, metabolic disorders,
febrile illnesses, or medication
use. Use of medications may
afect one or more components
of human thermoregulation
and induce hyperhidrosis.
Hyperhidrosis beginning later
in life should prompt a search
for secondary causes such
June 2012 | Midlife and Beyond | GM
22 Dermatology
Box 2: Secondary causes of hyperhidrosis
Generalised hyperhidrosis
(an area >100 square cm)
• Afecting almost any skin area
• Starts at older age
• Symmetry is not very distinctive
• Could be related to secondary causes, including medications
and systemic disorders
Localised hyperhidrosis
(an area <100 square cm)
• Afects axillae more than hands
• Starts at early age (<25) and improve later (>50)
• Usually bilaterally symmetrical
• Tends to cease during sleep
• Mainly related to autonomic dysfunction.
1. Neurologic or neoplastic diseases
2. Spontaneous periodic hypothermia and hyperhidrosis
3. Metabolic disorders or processes: thyrotoxicosis, diabetes
mellitus, hypoglycemia, gout, pheochromocytoma,
menopause
4. Febrile illnesses
5. Medications: propranolol, physostigmine, pilocarpine,
tricyclic antidepressants, and serotonin reuptake inhibitors.
6. Chronic alcoholism
7. Hodgkin disease or tuberculosis (causing nocturnal
hyperhidrosis)
1)
Gustatory stimuli:
• Seen in Frey syndrome, encephalitis, syringomyelia, diabetic
neuropathies, herpes zoster parotitis, and parotid abscess
2) Eccrine nevus & Blue rubber-bleb nevus
3) Eccrine angiomatous hamartoma*
4) Glomus tumor
5) POEMS syndrome: Peripheral neuropathy, organomegaly,
endocrinopathy, monoclonal plasma-proliferative disorder, and
skin changes.
6) Burning feet syndrome
7) Pachydermoperiostosis
8) Pre-tibial myxoedema
*
A rare benign malformation characterised by both eccrine and vascular
components, usually frst evident at birth or during early infancy as a
nodule/plaque, usually solitary, involving acral skin and although it
is ofen asymptomatic, it may be associated with focal hyperhidrosis,
hypertrichosis, and pain.
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as systemic diseases, adverse
effects of medication use, or
metabolic disorders. Secondary
causes may include endocrine
diseases such as diabetes
mellitus, hyperthyroidism, and
hyperpituitarism. 8 In one series,
one third of cases were neurologic
in origin, including peripheral
nerve injury, Parkinson disease,
reflex sympathetic dystrophy,
spinal injury, and Arnold-Chiari
malformation.9 Other secondary
causes to be considered may
include pheochromocytoma,
respiratory disease, and
psychiatric disease (Box 2).
Asymmetric hyperhidrosis may
suggest neurologic disease. 9
Primary hyperhidrosis usually
starts during adolescence or even
before and seems to be inherited
as an autosomal dominant genetic
trait. Primary hyperhidrosis
must be distinguished from
secondary
hyperhidrosis,
which can start at any point
in life. Primary hyperhidrosis
can be differentiated from
secondary type by certain clinical
criteria (Box 3). These criteria
discriminate well between the two
types (sensitivity: 0.99; specifcity:
0.82; positive predictive value:
0.99; negative predictive value:
0.852) and may facilitate
optimal clinical management. 10
Essential hyperhidrosis is a
dermatologic and neurologic
disorder characterised by
excessive sweating of the eccrine
sweat glands. 11 It is a disorder
of the eccrine sweat glands and
is associated with sympathetic
Essential
o v e r a c t i v i t y . 12
hyperhidrosis does not appear to
be a generalised disorder involving
vascular endothelium. Patients
note excessive sweating in afected
areas, which ultimately prompts
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24 Dermatology
Box 3: Criteria for the clinical diagnosis of primary (idiopathic)
hyperhidrosis
ii.
Diagnostic criteria favouring primary hyperhidrosis:
• Excessive sweating of six months or more in duration,
with four or more of the following:
1. Primarily involving eccrine-dense (axillae/palms/soles/
craniofacial) sites
2. Bilateral and relatively symmetric sweating
3. Cessation of sweating during sleep (absent nocturnally)
4. At least one episode per week
5. Onset at 25 years of age or younger
6. Family history of idiopathic hyperhidrosis (positive family
history)
7. Impairing daily activities.
them to seek medical attention.
Palmoplantar hyperhidrosis,
excessive sweating of the palms
and soles, is observed in persons
with chronic alcoholism and
it could be inherited in an
autosomal dominant manner.13,14
Clinical assessment
Diagnosis of this potentially
embarrassing and socially
disabling condition is based on
the patient’s history and visible
signs of sweating. Clinical
examination may be normal,
but will often reveal obvious
areas of focal sweating or
skin maceration. The primary
objective of clinical examination
is to reveal any evidence of
underlying chronic illness
suggestive of a secondary cause,
for example lymphadenopathy.
The main aims of clinical
assessment should be:
1. Identifying anatomical sites
with excessive sweating
2. Ensure the absence of
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physical findings suggestive
of secondary hyperhidrosis.
Investigation
Laboratory tests are not required
to make a diagnosis of primary
hyperhidrosis, but they only
serve to rule out and work-up
potential secondary causes of
excessive sweating. A number
of specialised tests have been
developed that quantify both
sweat production and the
impact on quality of life, such
as starch iodine test. However,
they are not required, nor are
they particularly useful in the
clinical setting. The work-up
for generalised sweating or
secondary hyperhidrosis can be
complicated, and often includes
a number of investigations.
Laboratory studies
Important laboratory studies in
the hyperhidrosis workup may
include the following:
i. Thyroid function tests
iii.
iv.
v.
may reveal underlying
hyperthyroidism
or
thyrotoxicosis
Blood glucose levels may
reveal diabetes mellitus or
hypoglycaemia
Urinary catecholamines
may reveal a possible
pheochromocytoma
Uric acid levels may reveal
gout
Screening
test
for
tuberculosis, such as purifed
protein derivative (PPD) test.
Imaging studies
Chest radiography may be
used to rule out tuberculosis
or a neoplastic cause of the
hyperhidrosis.
Management
Therapy for hyperhidrosis can be
challenging for both the patient
and the physician. Both topical
and systemic medications have
been used in the treatment of
hyperhidrosis. Other treatment
options for hyperhidrosis
include iontophoresis and
botulinum toxin injections. In
addition to pharmacological
therapy, other treatments
include surgical sympathectomy,
surgical excision of the affected
areas, and subcutaneous
liposuction. Each modality could
be used effectively. In general,
management of hyperhidrosis
should follow a gradational
step-wise approach, beginning
first with the least invasive
therapies and transitioning to
progressively more invasive
treatments for those patients
who fail. The appropriate
treatment will differ for each
patient, and will depend on the
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Dermatology 25
Box 4: Terapy options for hyperhidrosis (starting with the least invasive)
Afected area
Topical
therapy
Axillae
Face/head
Palms/hands
Feet/soles
Groin
Generalised
√
√
√
√
√
Systemic
therapy
√
Treatment options
Focal
Surgery
Botulinum (ETS
injections
& others)
√
√
√
√
√
√
√
√
Subcutaneous
liposuction &
laser therapy
√
√
location of focal hyperhidrosis,
the severity and patient tolerance
(Box 4).
Pharmacolological
therapy
Topical medications
Topical agents for hyperhidrosis
therapy include topical
anticholinergics, boric acid, 2-5%
tannic acid solutions, resorcinol,
potassium permanganate,
formaldehyde, glutaraldehyde,
and methenamine.15 All of these
agents are limited by staining,
contact sensitisation, irritancy,
or limited efectiveness. Because
of the limitations of other
agents, Drysol, a 20% aluminum
chloride hexahydrate in absolute
anhydrous ethyl alcohol, is more
commonly used as the frst-line
topical agent. 16 Drysol should
be applied nightly on dry skin
until a positive result is obtained,
afer which the intervals between
applications may be lengthened.
To minimise irritation, the
remainder of the medication
should be washed of when the
patient awakes, and the area may
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Iontophoresis
be neutralised with the topical
application of baking soda. 16
Aluminum chloride (frequently
used in antiperspirants) is
thought to obstruct sweat pores
and induce atrophy of secretory
cells within the sweat glands.
The only contraindication to
this treatment is documented
hypersensitivity, and aluminum
chloride should not be used on
irritated, broken, or recently
shaven skin. In addition, axillary
hyperhidrosis may be treated
with aluminium chloride gel,
although the gel may cause mild
cutaneous irritation.17
Systemic medications
Systemic agents used to
treat hyperhidrosis include
anticholinergic medications,
such as propantheline bromide,
glycopyrrolate, oxybutynin, and
benztropine. These agents are
efective because the preglandular
neurotransmitter for sweat
secretion is acetylcholine;
although the sympathetic nervous
system innervates the eccrine
sweat glands. 18,19 However, the
use of anticholinergics is limited
because their adverse effect
profile may include mydriasis,
blurring of vision, dry mouth and
eyes, difculty with micturition,
and constipation. However,
other systemic medications, such
as sedatives and tranquilisers,
indomethacin, and calcium
channel blockers, may be
beneficial in the treatment of
palmo-plantar hyperhidrosis.
Other therapies
Iontophoresis
Iontophoresis consists of passing a
direct current across the skin.20 Te
exact mechanism of action remains
under debate.21,22 In palmo-plantar
hyperhidrosis, the daily treatment
of each palm or sole for 30 minutes
at 15-20mA with tap water
iontophoresis is efective.23 Intact
skin can endure 0.2-mA/cm2
galvanic current without negative
consequences, and as much as 20–
25mA per palm may be tolerated.23
Numerous agents have been
used in iontophoresis to induce
hypohidrosis, including tap water
and anticholinergics; however,
treatment with anticholinergic
iontophoresis is more effective
than tap water iontophoresis.24
June 2012 | Midlife and Beyond | GM
26 Dermatology
Botulinum toxin
Botulinum toxin injections
are effective because of their
anticholinergic effects at the
neuromuscular junction and in
the postganglionic sympathetic
cholinergic nerves in the sweat
glands. 25,26,27 Adverse effects
of intradermal injections of
botulinum A toxin may result
from diffusion into underlying
muscles.28,29 Treatment of axillary
hyperhidrosis with botulinum
toxin type A reconstituted in
lidocaine was associated with
less pain (from the injection)
when compared with the one
reconstituted in normal saline.30
The results were the same in
the two groups, thus, lidocainereconstituted botulinum toxin
A may be preferable for treating
axillary hyperhidrosis. In cases
with palmar hyperhidrosis,
multiple (50) subepidermal
injections result in anhydrosis
lasting 4–12 months, and each
injection produces an area of
anhydrosis approximately 1.2cm
in diameter.31 Te only adverse
effect is mild transient thumb
weakness that resolves within
three weeks.
Surgical treatment
Sympathectomy
Sympathectomy has been used as
a permanent efective treatment
for almost 90 years. It is usually
reserved for the fnal treatment
Sympathectomy
o p t i o n . 32
involves the surgical destruction
of the ganglia responsible
for hyperhidrosis, T2 and T3
thoracic ganglia in palmar
hyperhidrosis, T4 thoracic
ganglia in axillary hyperhidrosis,
and T1 thoracic ganglia in facial
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hyperhidrosis.33,34,35 Two surgical
approaches are available: an open
approach and a newer endoscopic
approach, such as endoscopic
thoracic sympathectomy (ETS).
The endoscopic approach has
become favored because of
its improvements in terms of
complications, surgical scars,
and surgical times. In palmar
hyperhidrosis, a survey showed
thoracoscopic sympathectomy
to be minimally invasive and
to improve the patient’s quality
of life, even if compensatory
hyperhidrosis occurs.36 Numerous
complications are associated
with the endoscopic treatment
option; including compensatory
sweating (induction of sweating
in previously unafected areas of
the body), gustatory sweating,
pneumothorax, intercostal
neuralgia, Horner syndrome,
recurrence of hyperhidrosis, and
the sequelae of using general
anesthetic. Topical glycopyrrolate
application may be efective and
safe for the treatment of excessive
facial sweating in primary
craniofacial and secondary
gustatory hyperhidrosis following
s y m p a t h e c t o m y . 37 L u m b a r
sympathectomy is a relatively new
procedure aimed at those patients
for whom ETS has not relieved
excessive plantar sweating. The
success rate is about 90% and the
operation should be carried out
only if patients first have tried
other conservative measures.38
Other surgical techniques
Surgical excision of the afected
area identifed using iodine starch
testing, removes the appropriate
sweat glands, thereby eliminating
sweating. This technique is
particularly useful in axillary
hyperhidrosis.
Subcutaneous liposuction is
another means of removing the
eccrine sweat glands responsible
for axillary hyperhidrosis.
Compared with classic surgical
excision, this modality results in
less disruption to the overlying
skin, resulting in smaller surgical
scars and a diminished area of
hair loss.39
Laser treatment of axillary
hyperhidrosis using the 1064-nm
Nd-YAG laser was found to be
efective and safe as well.40
Conclusion
Hyperhidrosis is a condition
in which excess sweating
affects various parts or the
whole body. The condition
usually is idiopathic and can be
secondary to various disorders or
medications use. Hyperhidrosis
beginning later in life should
prompt a search for secondary
causes, including systemic
diseases and adverse effects of
certain medications. Treatment
options for hyperhidrosis
include
topical
agents,
iontophoresis and botulinum
toxin injections. In addition
to pharmacologic therapy,
endoscopic sympathectomy and
surgical excision of the afected
areas have been used. However,
the condition is difcult to treat
efectively and a logical approach
must be taken to individualise
therapy based on the degree of
functional impairment.
Conflict of interest: none
declared
References available on online
version at www.gmjournal.
co.uk
www.gerimed.co.uk